{
  "abstract": "Chimeric antigen receptor-natural killer (CAR-NK) cells combine innate cytotoxicity with antigen-directed killing and promise as an immunotherapy with lower cytokine toxicity than CAR-T approaches. However, clinical translation is limited by challenges in transduction, persistence, tumor infiltration, and the immunosuppressive tumor microenvironment (TME). We performed a comprehensive literature review of recent preclinical and early-phase clinical studies, engineering strategies (CAR design, transduction technologies, gene-editing), manufacturing and expansion protocols, and trial outcomes in this review. We noted a reference to the advantages of CAR-NK, like multimodal killing (CAR-dependent and innate pathways), potential for allogeneic \"off-the-shelf\" use, and favorable early safety profiles. However, NK-specific obstacles persist: lower viral transduction efficiencies, short in vivo persistence, poor infiltration into solid tumors, and TME-mediated suppression (TGF-β, adenosine, metabolic stress). Engineering countermeasures such as IL-15 expression, checkpoint receptor knockout, chemokine receptor co-expression (e.g., CXCR1/4), DAP10/DAP12-based signaling domains, and non-viral delivery (transposons/CRISPR) have shown preclinical promise. CAR-NK therapy has developed from concept to a clinically actionable treatment line for hematologic malignancies and shows emerging potential in solid tumors when combined with TME-modulating strategies. This review provides robust evidence about CAR-NK therapies in hematological and solid tumors, with a great emphasis on the challenges they encounter, strategies, and innovative approaches to overcome these challenges, and forward-looking perspectives to improve future therapeutic CAR-NK designs and clinical outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Medicine, Benha National University, Obour, Egypt.",
    "Faculty of Medicine, Benha National University, Obour, Egypt. nour10503@med.bnu.edu.eg.",
    "Faculty of Medicine, Alexandria University, Alexandria, Egypt.",
    "Faculty of Medicine, Tanta University, Tanta, Egypt.",
    "Allama Iqbal Medical College, Lahore, Pakistan.",
    "Assistant Professor of Surgery, Director of Breast Surgical Services, Texas Tech University Health Sciences Center, El Paso, USA."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Salma Mohamed Awadallah"
    },
    {
      "affs": [
        1
      ],
      "name": "NourEldin Elmesalamy",
      "orcid": "0009-0003-9502-9964"
    },
    {
      "affs": [
        2
      ],
      "name": "Ahmed Reda Bahr",
      "orcid": "0009-0001-8719-4738"
    },
    {
      "affs": [
        3
      ],
      "name": "Basant Atef",
      "orcid": "0009-0003-6665-0778"
    },
    {
      "affs": [
        4
      ],
      "name": "Eeman Afroz"
    },
    {
      "affs": [
        5
      ],
      "name": "Hank C Hill"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/09ecsaf5fessj.bib",
  "cited_by": 0,
  "doi": "10.1007/s00432-026-06635-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13695643",
  "id": "09ecsaf5fessj",
  "issns": [
    "0171-5216",
    "1432-1335"
  ],
  "landing_url": "https://europepmc.org/article/MED/42926223",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223305032",
  "pdf_url": "https://europepmc.org/articles/PMC13695643?pdf=render",
  "pmcid": "PMC13695643",
  "pmid": "42926223",
  "published": "2026-10-23",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/09ecsaf5fessj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42926223",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42926223"
    },
    {
      "first_seen": "2026-10-30T13:45:39Z",
      "native_id": "effeb0c7592046a189406376d0504a53",
      "source": "doaj",
      "url": "https://doi.org/10.1007/s00432-026-06635-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "CAR-NK cell immunotherapy: a comprehensive review of engineering platforms, clinical applications in hematological and solid tumors.",
  "title_text": "CAR-NK cell immunotherapy: a comprehensive review of engineering platforms, clinical applications in hematological and solid tumors.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:39Z",
  "url": "https://research.draconitic.com/paper/09ecsaf5fessj",
  "venue": "Journal of cancer research and clinical oncology",
  "versions": []
}